Liquid crystalline mesophases based on glycerol monooleate (GMO, also known as monoolein, monoglyceride) are the subject of an ongoing scientific research due to their complex structural features and various potential applications. These systems are characterized by a high internal ordering and symmetry as well as by a vast interfacial area and the existence of both hydrophobic and hydrophilic domains. These structural properties make lyotropic liquid crystals (LLC) promising candidates for research and applications in drug delivery, food systems and the synthesis of template-ordered materials. The common and well-studied LLC phases are the lamellar (Lα), hexagonal (normal, HI or inverted HII) and normal or inverted cubic (bicontinuous or micellar) structures.
Significant progress has been made during the last decade in the characterization of interactions of proteins with cubic LLC, mainly for crystallographic and drug delivery purposes. Cubic phase was successfully used for entrapment and crystallization of several membrane proteins for single crystal X-ray crystallography goals. Hydrophilic proteins such as lysozyme, cytochrome C, hemoglobin and insulin were solubilized into the cubic phase.
While the mutual interplay of the cubic phase components, including the phase behavior and the structural conformations of the proteins, was demonstrated and discussed, the understanding of the interactions of proteins with reverse hexagonal mesophases (HII) that are involved in different biological processes like membrane fusion, and might be found in cellular and intracellular membranes is lacking.
HII mesophases consist of cylindrical surfactant micelles arranged on a two-dimensional hexagonal lattice. These structures can accommodate hydrophilic, hydrophobic and amphiphilic guest molecules either within the aqueous compartments, composed of dense packed, straight water-filled cylinders, or by direct interaction within the lipid hydrophobic moieties, orientated radially outward from the centers of the water rods [1, 2]. Furthermore, lower viscosity of these mesophases, compared to the highly viscous cubic phase, is advantageous for practical applications.
While the HII mesophase based only on monoolein and water existed in elevated temperatures (the cubic phase is transformed into the HII mesophase only at ca. 85° C.) and hence could not have been used for solubilization of peptides and proteins, recently the ability of triacylglycerols (triglycerides, TAG) to promote existence of HII phases at room temperature was investigated. It was found that TAGs with medium-chain fatty acids transformed lamellar and cubic phases into a hexagonal mesophase that remains stable at room temperature [3]. This finding enabled the solubilization of biomacromolecules into the mesophase and their utilization as drug delivery vehicles and also as matrices for chemical and enzymatic reactions.
Physical properties of ternary GMO/tricaprylin/water HII mesophases were extensively studied. Furthermore, it was demonstrated that lipophilic peptide drug cyclosporine A and hydrophilic desmopressin were solubilized into the HII mesophases [4]. The effect of their incorporation on the mesophases, as well as the structural conformations of the peptides were studied both on a macroscopic and molecular levels.